A Study of R1507 in Participants With Recurrent or Refractory Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

This study will evaluate the efficacy and safety of R1507 in participants with recurrent or refractory sarcoma. Eight cohorts of sarcoma participants will be studied in parallel. Cohort 1: Ewing's sarcoma primary cohort defined as participants who have relapsed less than or equal to (<=) 24 months from diagnosis, received at least two prior chemotherapy programs and are unresectable. Cohort 2: Ewing's sarcoma non-primary (secondary) cohort defined as participants who have relapsed greater than or equal to (>=) 24 months from diagnosis or have only received one prior chemotherapy program. Cohort 3: Expanded Ewing's sarcoma defined as participants with recurrent or relapse regardless of prior number of salvage regimens and regardless of time of relapse. Cohort 4: participants with osteosarcoma. Cohort 5: Participants with synovial sarcoma. Cohort 6: Participants with rhabdomyosarcoma Cohort 7: Participants with alveolar soft part sarcoma (7a), desmoplastic small round cell tumors (7b), extraskeletal myxoid chondrosarcoma (7c), clear cell sarcoma (7d), myxoid liposarcoma (7e). Cohort 8: Participants with unspecified sarcoma diagnosis. Participants in the expanded Ewing's sarcoma Cohort 3 will receive 27 milligrams (mg)/kilogram (kg) every 3 weeks intravenously (IV). All other participants will receive R1507 9 mg/kg IV weekly. The anticipated time on study treatment is until disease progression or unacceptable adverse events, withdrawal or death.

A Phase II Trial of R1507, a Recombinant Human Monoclonal Antibody to the Insulin-Like Growth Factor-1 Receptor for the Treatment of Participants With Recurrent or Refractory Ewing's Sarcoma, Osteosarcoma, Synovial Sarcoma, Rhabdomyosarcoma and Other Sarcomas.

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 1 includes individuals with Ewing's sarcoma who have relapsed within 24 weeks after diagnosis and have received two or more prior chemotherapy regimens.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 2: Ewing's Sarcoma Secondary Cohort

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 2 includes individuals with Ewing's sarcoma who have relapsed more than 24 weeks after diagnosis and have only received one prior chemotherapy regimen.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 3: Ewing's Sarcoma Expanded Cohort

Participants 2 to 21 years of age with recurrent or refractory sarcoma receive R1507 as 27 mg/kg via IV infusion every 3 weeks until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 3 includes individuals with Ewing's sarcoma who were enrolled and treated following safety evaluation in other cohorts.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 4: Osteosarcoma

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 4 includes individuals with osteosarcoma.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 5: Synovial Sarcoma

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 5 includes individuals with synovial sarcoma.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 6: Rhabdomyosarcoma

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 6 includes individuals with rhabdomyosarcoma.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 7a: Alveolar Soft Part Sarcoma

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7a includes individuals with alveolar soft part sarcoma.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 7b: Desmoplastic Small Round Cell Tumors.

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7b includes individuals with desmoplastic small round cell tumors.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 7c: Extraskeletal Myxoid Chondrosarcoma

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7c includes individuals with extraskeletal myxoid chondrosarcoma.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 7d: Clear Cell Sarcoma

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7d includes individuals with clear cell sarcoma.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 7e: Myxoid Liposarcoma

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 7e includes individuals with myxoid liposarcoma.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Experimental: Cohort 8: Diagnosis Not Specified

Participants 2 years of age and older with recurrent or refractory sarcoma receive R1507 as 9 mg/kg via IV infusion once weekly until disease progression, intercurrent illness, unacceptable toxicity, prolonged (2-week) time off treatment, withdrawal, loss to follow-up, investigator decision, or death. Cohort 8 includes individuals with subtypes of sarcoma not specified in the protocol.

Drug: RG1507

Participants will receive R1507 IV infusion as 9 mg/kg once weekly or 27 mg/kg every 3 weeks, depending upon the cohort in which the participants are enrolled.

Percentage of Participants with Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8 [ Time Frame: Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression) ]

Progression-Free Survival (PFS) According to WHO Response Criteria at 18 weeks from Start of R2607 Treatment in Cohort 1 [ Time Frame: Baseline up to 18 weeks (assessed at baseline, every 6 weeks until disease progression) ]

Percentage of Participants with Adverse Events (AEs) in Cohort 1 and 2 [ Time Frame: Baseline up to 6 years ]

Secondary Outcome Measures
:

Duration of Response (DOR) According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

Time to Progression (TTP) According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

Failure-Free Survival (FFS) According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

Overall Survival (OS) in Cohorts 2 to 8 [ Time Frame: Baseline until death (up to 6 years) ]

PFS According to WHO Response Criteria at 18 Weeks from Start of R1507 Treatment in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks until disease progression (up to 18 weeks) ]

PFS According to WHO Response Criteria in Cohorts 2 to 8 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

Percentage of Participants with Complete or Partial Response According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

TTP According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

FFS According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

DOR According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

PFS According to WHO Response Criteria in Cohort 1 [ Time Frame: Baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression (up to 6 years) ]

OS in Cohort 1 [ Time Frame: Baseline until death (up to 6 years) ]

Percentage of participants with AEs in all Cohorts [ Time Frame: Baseline up to 6 years ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.